SPPL3
Description
The SPPL3 (signal peptide peptidase like 3) is a protein-coding gene located on chromosome 12.
SPPL3 is an intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane protein substrates in or close to their luminal transmembrane domain boundaries. It acts like a sheddase by mediating the proteolytic release and secretion of active site-containing ectodomains of glycan-modifying glycosidase and glycosyltransferase enzymes such as MGAT5, B4GAT1 and B4GALT1. SPPL3 catalyzes the intramembrane cleavage of the envelope glycoprotein gp130 and/or the leader peptide gp18LP of the simian foamy virus independent of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis. It may also have the ability to serve as a shedding protease for subsequent intramembrane proteolysis by SPPL2A and SPPL2B of the envelope glycoprotein gp130. SPPL3 plays a role in the regulation of cellular glycosylation processes. It is required to link T-cell antigen receptor (TCR) and calcineurin-NFAT signaling cascades in lymphocytes by promoting the association of STIM1 and ORAI1 during store-operated calcium entry (SOCE) in a protease-independent manner.
SPPL3 is also known as IMP2, MDHV1887, PRO4332, PSH1, PSL4.
